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Houman Ashrafian

Publications and source records attributed to Houman Ashrafian.

At least 19 recordsLinked to original sources
PubMed2007

Regression of dilated-hypokinetic hypertrophic cardiomyopathy by biventricular cardiac pacing.

The evolution of hypertrophic cardiomyopathy (HCM) towards dilatation and hypokinesis is an increasingly recognized complication with a high incidence of adverse outcomes, including sudden cardiac death, requiring defibrillator implantation and cardiac transplantation. It is generally regarded as the irreversible 'burnt-out' end-stage manifestation of HCM. We report one of the first cases of profound regression of the dilated-hypokinetic state by the application of biventricular pacing and cardiac resynchronization therapy (CRT). Reviewing the literature on the role of pacing in HCM and the energetic rationale for CRT in HCM prompts us to suggest that further systematic studies are needed urgently to assess the role of CRT in HCM variants.

Adult↗
PubMed2006

Cancer's sweet tooth: the Janus effect of glucose metabolism in tumorigenesis.

Despite Otto Warburg's 1931 Nobel Prize for his work affirming the role of metabolism in carcinogenesis, there has been little further interest in this association between metabolism and cancer. Disinterest has, in part, been attributable to the notion that Warburg's description of a relation between a shift to glycolysis in carcinogenesis may be an epiphenomenon rather than a mechanistic determinant. By studying the critical cellular energy sensor AMP-activated protein kinase (AMPK), I postulate that the association between intermediary metabolism and tumours varies over time. Through accumulation of carbohydrates and pan-inhibition of AMPK, premalignant tumours may gain a replicative advantage through the repression of senescence. Conversely, malignant tumours, with a defective tumour suppressor contingent, undergo a "glycolytic switch", in part by tolerating a degree of AMPK activation, to mitigate substrate limitation. I contend that this Janus-faced relation with intermediary metabolism contributes to carcinogenesis; if proven, this finding would have important implications for public health, in that it would lend support to the idea that prevention of obesity, and caloric restriction and exercise could reduce the predisposition to cancer.

AMP-Activated Protein Kinases↗
PubMed2005

Metabolic modulation with perhexiline in chronic heart failure: a randomized, controlled trial of short-term use of a novel treatment.

BACKGROUND: Chronic heart failure (CHF) is a major cause of morbidity and mortality that requires a novel approach to therapy. Perhexiline is an antianginal drug that augments glucose metabolism by blocking muscle mitochondrial free fatty acid uptake, thereby increasing metabolic efficiency. We assessed the effects of perhexiline treatment in CHF patients. METHODS AND RESULTS: In a double-blind fashion, we randomly assigned patients with optimally medicated CHF to either perhexiline (n=28) or placebo (n=28). The primary end point was peak exercise oxygen consumption (VO2max), an important prognostic marker. In addition, the effect of perhexiline on myocardial function and quality of life was assessed. Quantitative stress echocardiography with tissue Doppler measurements was used to assess regional myocardial function in patients with ischemic CHF. 31P magnetic resonance spectroscopy was used to assess the effect of perhexiline on skeletal muscle energetics in patients with nonischemic CHF. Treatment with perhexiline led to significant improvements in VO2max (16.1+/-0.6 to 18.8+/-1.1 mL . kg(-1) . min(-1); P<0.001), quality of life (Minnesota score reduction from 45+/-5 to 34+/-5; P=0.04), and left ventricular ejection fraction (24+/-1% to 34+/-2%; P<0.001). Perhexiline treatment also increased resting and peak dobutamine stress regional myocardial function (by 15% and 24%, respectively) and normalized skeletal muscle phosphocreatine recovery after exercise. There were no adverse effects during the treatment period. CONCLUSIONS: In patients with CHF, metabolic modulation with perhexiline improved VO2max, left ventricular ejection fraction, symptoms, resting and peak stress myocardial function, and skeletal muscle energetics. Perhexiline may therefore represent a novel treatment for CHF with a good safety profile, provided that the dosage is adjusted according to plasma levels.

Aged↗
PubMed2005

Beta-blocker therapy of cardiovascular diseases in patients with bronchial asthma or COPD: the pro viewpoint.

Extensive randomised clinical trial data support the view that beta-blockers have a significant impact on the prognosis of patients with cardiovascular disease, especially those with coronary artery disease and chronic heart failure. Unfortunately, this essential treatment is often withheld from patients with asthma and from some patients with Chronic Obstructive Pulmonary Disease (COPD). The principal concern, a concern supported by a number of guidelines, is that beta-blockers may precipitate severe and potentially fatal bronchospasm. However, a number of studies, culminating in a recent meta-analysis, show that cardioselective beta-blockers are not only safe but are beneficial in patients with co-existing airways and coronary disease. In this article we review the evidence supporting the position that cardioselective beta-blockers, when introduced with care in both community and hospital settings, are safe in patients with mild airways disease and can significantly improve prognosis.

Journal Article↗
PubMed2005

Increased left atrial volume index is an independent predictor of raised serum natriuretic peptide in patients with suspected heart failure but normal left ventricular ejection fraction: Implication for diagnosis of diastolic heart failure.

BACKGROUND: Left atrial volume index (LAVI) is increasingly recognised as a relatively load-independent marker of left ventricular (LV) filling pressures. We assessed the capacity of LAVI to predict LV diastolic dysfunction in comparison with N-terminal pro B-type natriuretic peptide (NTproBNP) in patients with suspected heart failure and a normal ejection fraction (EF). METHODS: 137 patients with suspected heart failure (HF), referred from the community for echocardiography, prospectively underwent Doppler echocardiography, LAVI and NTproBNP estimation. Raised LAVI and reduced LV systolic function were defined as >26 ml/m2 and LV EF <50% respectively. RESULTS: Of 137 patients, 21 were excluded (2 with significant mitral valve disease and 19 with atrial fibrillation). Of the remaining 116 subjects, 92 showed normal LV systolic function. The univariate predictors of serum log NTproBNP were age (p < 0.001), LA dimension (p = 0.001), LAVI (p < 0.001), A wave (p = 0.001), E:A (p = 0.07) and septal wall thickness (p = 0.004). However on multivariate analysis, LAVI was found to be the most consistent and significant predictor of NTproBNP. The area under the curve of the receiver operating characteristic (ROC) curve for NTproBNP in detecting patients with LVEF > or = 50% and LAVI >26 ml/m2 was 0.81 (p < 0.0001) and for patients with LAVI > 26 ml/m2 with and without LVEF > or = 50% was 0.82 (p < 0.0001). CONCLUSION: This data confirms that LAVI on resting echocardiography, specifically in patients with suspected HF and normal LV systolic function is a powerful independent predictor of LV diastolic dysfunction as predicted by serum NTproBNP. In a population with a high suspicion of diastolic heart failure, LAVI may significantly contribute to diagnostic precision.

Aged↗
PubMed2004

The natriuretic peptides and their role in disorders of right heart dysfunction and pulmonary hypertension.

Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are increased in conditions with cardiac ventricular volume and pressure overload. The general physiological and potential therapeutic roles of natriuretic peptides in respiratory disease, right ventricular (RV) dysfunction, and pulmonary arterial hypertension (PAH) are reviewed. BNP levels can be used to differentiate between dyspneic patients with a pure respiratory defect and those with RV dysfunction. BNP levels also correlate with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) in patients with PAH (atrial septal defect, chronic thromboembolic disease, and scleroderma). BNP is a predictor of mortality in patients with primary pulmonary hypertension (PPH). These are important clinical implications in that a noninvasive blood test may be used to identify high-risk patients for more invasive procedures such as cardiac catheterization. BNP or NT-proBNP measurements may also be used to guide therapy (e.g., pulmonary vasorelaxants) in PAH since upregulation of the natriuretic peptide pathway has been shown to reduce cardiac hypertrophy and PAH. Additionally, there may be therapeutic potential via recombinant BNP or neutral endopeptidase inhibitors in RV dysfunction and PAH.

Animals↗
PubMed2004

Natriuretic peptides, respiratory disease, and the right heart.

It is well-recognized that atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are raised in conditions with ventricular volume and pressure overload. In addition to this established role in left ventricular congestive cardiac failure, there is good evidence that BNP has a diagnostic role in right ventricular (RV) dysfunction and pulmonary arterial hypertension (PAH). For example, BNP levels can be used to differentiate between dyspneic patients with pure respiratory defects and those with RV dysfunction. Studies in patients with PAH have demonstrated significant correlations between BNP levels and mean pulmonary arterial pressure as well as pulmonary vascular resistance. Additionally, BNP has a prognostic role in patients with RV pressure overload and pulmonary hypertension, and it offers a noninvasive test that can be used to guide therapy in patients with PAH. However, although measured plasma proBNP levels are raised in conditions with RV overload, its biological significance is still not well-understood. In this article, we review the general physiologic and potential therapeutic role of natriuretic peptides in respiratory disease, RV dysfunction, and PAH. Furthermore, we assess the various clues toward natriuretic peptide action coming from laboratory studies. ANP and BNP knockout mice develop cardiac fibrosis and hypertrophy. Potentiation of the natriuretic pathway has been shown to reduce cardiac hypertrophy and PAH. This is likely to take place as a result of increased intracellular cyclic guanosine monophosphate levels and subsequent pulmonary vasorelaxant activity. In view of this evidence, there may be a rationale for the therapeutic use of recombinant BNP or neutral endopeptidase inhibitors under conditions of RV dysfunction and PAH.

Animals↗
PubMed2003

Hypertrophic cardiomyopathy:a paradigm for myocardial energy depletion.

Genetic analysis of hypertrophic cardiomyopathy (HCM), a mendelian form of cardiac hypertrophy, indicates that the primary defect is in sarcomeric function. However, the initial proposal that depressed myocardial contraction leads to a 'compensatory' hypertrophy has proven inconsistent with laboratory and clinical evidence. Drawing on observations of mutant contractile protein function, together with mouse models and clinical studies, we propose that sarcomeric HCM mutations lead to inefficient ATP utilization. The suggestion that energy depletion underlies HCM is supported by the HCM-like phenotype found with mutations in a variety of metabolic genes. A central role for compromised energetics would also help explain the unresolved clinical observations of delayed onset and asymmetrical hypertrophy in HCM, and would have implications for therapy in HCM and, potentially, in more-common forms of cardiac hypertrophy and failure.

Adenosine Triphosphate↗